NETosis Markers in Pregnancy: Effects Differ According to Histone Subtypes

Sylvie Bouvier; Mathieu Fortier; Laura Vincent; Christophe Demattei; Eve Mousty; Marielle Herzog; Guillaume Rommelaere; Eva Nouvellon; Eric Mercier; Vincent Letouzey; Jean-Christophe Gris

doi:10.1055/s-0040-1722225

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2021; 121(07): 877-890
DOI: 10.1055/s-0040-1722225

Coagulation and Fibrinolysis

NETosis Markers in Pregnancy: Effects Differ According to Histone Subtypes

Sylvie Bouvier ^*

¹Department of Haematology, University Hospital, Nîmes, France

²Research Laboratory EA 2992, Montpellier University, Montpellier, France

³Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France

,

Mathieu Fortier‡^*

¹Department of Haematology, University Hospital, Nîmes, France

,

Laura Vincent

¹Department of Haematology, University Hospital, Nîmes, France

,

Christophe Demattei

⁴Department of Biostatistics, Public Health and Innovation in Methodology, Nîmes University Hospital, Nîmes, France

,

Eve Mousty

⁵Department of Gynecology and Obstetrics, University Hospital, Nîmes, France

,

Marielle Herzog

⁶Belgian Volition SPRL, Parc Scientifique Crealys, Isnes, Belgium

,

Guillaume Rommelaere

⁶Belgian Volition SPRL, Parc Scientifique Crealys, Isnes, Belgium

,

Eva Nouvellon

¹Department of Haematology, University Hospital, Nîmes, France

²Research Laboratory EA 2992, Montpellier University, Montpellier, France

,

Eric Mercier

¹Department of Haematology, University Hospital, Nîmes, France

²Research Laboratory EA 2992, Montpellier University, Montpellier, France

³Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France

,

Vincent Letouzey

⁵Department of Gynecology and Obstetrics, University Hospital, Nîmes, France

⁷Department of Artificial Polymers, Max Mousseron Institute of Biomolecules, Montpellier University, Montpellier, France

,

Jean-Christophe Gris

¹Department of Haematology, University Hospital, Nîmes, France

²Research Laboratory EA 2992, Montpellier University, Montpellier, France

³Faculty of Pharmaceutical and Biological Sciences, Montpellier University, Montpellier, France

⁸Department of Gynecology, I. M. Sechenov First Moscow State Medical University, Moscow, Russian Federation

› Institutsangaben

Abstract

NETosis is an innate immune response occurring after infection or inflammation: activated neutrophils expel decondensed DNA in complex with histones into the extracellular environment in a controlled manner. It activates coagulation and fuels the risk of thrombosis. Human pregnancy is associated with a mild proinflammatory state characterized by circulatory neutrophil activation which is further increased in complicated pregnancies, placenta-mediated complications being associated with an increased thrombotic risk. This aberrant activation leads to an increased release of nucleosomes in the blood flow. The aim of our study was to initially quantify nucleosome-bound histones in normal pregnancy and in placenta-mediated complication counterpart. We analyzed the role of histones on extravillous trophoblast function. Circulating nucleosome-bound histones H3 (Nu.QH3.1, Nu.QH3PanCit, Nu.QH3K27me3) and H4 (Nu.QH4K16Ac) were increased in complicated pregnancies. In vitro using the extravillous cell line HTR-8/SVNeo, we observed that free recombinant H2B, H3, and H4 inhibited migration in wound healing assay, but only H3 also blocked invasion in Matrigel-coated Transwell experiments. H3 and H4 also induced apoptosis, whereas H2B did not. Finally, the negative effects of H3 on invasion and apoptosis could be restored with enoxaparin, a low-molecular-weight heparin (LMWH), but not with aspirin. Different circulating nucleosome-bound histones are increased in complicated pregnancy and this would affect migration, invasion, and induce apoptosis of extravillous trophoblasts. Histones might be part of the link between the risk of thrombosis and pregnancy complications, with an effect of LMWH on both.

Keywords

histones - NETosis - pregnancy - preeclampsia - trophoblast

Volltext

Referenzen

References
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